Stage 3 chronic kidney disease MedDRA version: 23.1 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: Balcinrenone
Product Code: AZD9977
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Balcinrenone
Current Sponsor code: 1850385-64-6
Other descriptive name: 2-{(3S)-7-fluoro-4-[(3-
Sponsors
Klinikum Nürnberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients over 50 years old 2. Diagnosis of chronic kidney disease, with eGFR =30 and =60 mL/min/1.73m2 3. Serum/ plasma K+ levels = 3.5 and =65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Diagnosis of type 1 diabetes mellitus 2. Uncontrolled type 2 diabetes mellitus with HbA1C > 10.5% in the most recent medical records 3. Participants with type 2 diabetes mellitus treated with insulin if insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) was not stable in the 12 weeks prior to randomization as judged by the Investigator 4. Patients with systolic blood pressure levels 2 × ULN (upper limit of normal); or total bilirubin levels (TBL) > 2 × ULN; or serum albumin levels < 3.5 g/dL 11. Medical conditions associated with development of hyperkalemia (Addison's disease) 12. Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within 3 months prior to screening 13. Hemoglobin levels below 8.5 g/dL or over 15 g/dL 14. Patients who have received an organ or bone marrow transplant 15. HIV infection 16. Active cancer, history of bladder cancer 17. Patients who have had major surgery in the 3 months prior to screening 18. Patients with muscular dystrophies 19. Patients who have severe comorbid conditions likely to compromise survival or study participation 20. Pregnant and breast-feeding women 21. Medical treatment with either a mineralocorticoid receptor antagonist (MRA) or a sodium-glucose co-transporter-2 inhibitor (SGLT2i) within 3 months prior to screening 22. Medical treatment with potassium binders 23. Medical treatment with strong or moderate CYP3A4 inducers or inhibitors 24. Prior serious hypersensitivity reaction to dapagliflozin (Forxiga®), balcinrenone or to any of their excipients 25. Treatment with cytotoxic therapy, immunosuppressive therapy or other immunotherapy within 6 months prior to screening 26. Unwillingness or other inability to cooperate 27. For patients undergoing MRI scans, presence of implanted devices (surgical clips, heart pacemakers or defibrillators, cochlear implants), iron-based tattoos, any other pieces of metal or devices that are not MRsafe anywhere in the body
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show that treatment with balcinrenone preserves the beneficial dapagliflozin-driven increase in 24h renal glucose excretion;Secondary Objective: Topic 1 To demonstrate that the dapagliflozin-induced increase in urine solute concentration is not altered by balcinrenone Topic 2 To demonstrate that treatment with dapagliflozin, with or without balcinrenone reduces free-water clearance within 48h, and further urine concentration is observed after 4 weeks, increases the contribution of glucose to osmotic-diuretic volume formation, decreases the contribution of sodium and urea to osmotic-diuretic volume formation, does not change the contribution of potassium to osmotic-diuretic volume formation within 48h, and that this effect persists after 4 weeks and does not change body water content after 4 weeks. Topic 3 To demonstrate that patients treated with dapagliflozin alone or in combination with balcinrenone show increased plasma copeptin levels and show increased plasma glucagon and reduced plasma insulin levels within 48h and/or after 4 weeks.;Primary end point(s): Change from baseline in 24h urine glucose excretion at day 3 and day 28;Timepoint(s) of evaluation of this end point: day 3 and day 28 (only day 28 for France) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Topic 1 • Change from baseline in urine osmolality at day 3 and day 28 Topic 2 • Change from baseline in free water clearance at day 3 and day 28 • Change from baseline in urine glucose fraction at day 3 and day 28 • Change from baseline in urine sodium fraction at day 3 and day 28 • Change from baseline in urine urea fraction at day 3 and day 28 • Change from baseline in urine potassium fraction at day 3 and day 28 • Change from baseline in muscle water content as measured at 7T MRI at day 28 Topic 3 • Change from baseline in copeptin levels at day 3 and day 28 • Change from baseline in plasma insulin/glucagon ratio at day 3 and day 28;Timepoint(s) of evaluation of this end point: day 3 and day 28 (only day 28 for France including muscle water content) | — |
Countries
France
Contacts
Public ContactCoordinating investigator
Klinikuù Nürnberg
Outcome results
None listed